It is generally difficult to achieve localization of aerosols in particular sites in the respiratory tract by conventional inhalation via the mouth. [Gonda, Pharmaceutical Inhalation Aerosol Technology (Ed. A. J. Hickey), Marcel Dekker, Inc., N.Y., pp. 61-82 (1992)]. Others have employed microspray equipment inserted into airways in animal studies and reported achieving good localization of the delivered dose. [Ferron et al., J. Aerosol Sci. 22, S867-S870 (1991); Kreyling et al., J. Aerosol Sci. 24, S451-S452 (1993); Hoover et al., J. Aerosol Med. 6, 67-72 (1993)]. In order to atomize the liquid they employed compressed air. Although no adverse reactions to the treatment were reported in their experimental animals, application to humans runs the risk of rapid gas expansion inside the airways, a result prudently to be avoided.
Previously, larger volumes of bulk liquid were administered by dripping the material into the airways through a conventional washing pipe that is inserted into the channel of a bronchoscope. However, this method may result in bulk fluid motion into the distal airways and alveoli that would be important to prevent in order to avoid adverse reactions such as inflammation, or infection in the case of gene transfer therapy using viral vectors.
Accordingly, it was an object of the present invention to deliver functional biologic materials in the form of liquid via a bronchoscope in order to achieve well defined localization of such biologic materials in human airways, where they would be expected to be readily available locally with minimal overspill into the alveoli.